Published Ahead of Print on January 3, 2018 as 10.1212/WNL.0000000000004888 ARTICLE OPEN ACCESS CLASS OF EVIDENCE Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease Motoki Fujimaki, MD, Shinji Saiki, MD, PhD, Yuanzhe Li, PhD, Naoko Kaga, PhD, Hikari Taka, PhD, Correspondence Taku Hatano, MD, PhD, Kei-Ichi Ishikawa, MD, PhD, Yutaka Oji, MD, Akio Mori, MD, Ayami Okuzumi, MD, Dr. Saiki Takahiro Koinuma, MD, Shin-Ichi Ueno, MD, Yoko Imamichi, BS, Takashi Ueno, PhD, Yoshiki Miura, PhD,
[email protected] Manabu Funayama, PhD, and Nobutaka Hattori, MD, PhD or Dr. Hattori
[email protected] Neurology® 2018;90:e1-8. doi:10.1212/WNL.0000000000004888 Abstract MORE ONLINE Objective ff Class of evidence To investigate the kinetics and metabolism of ca eine in serum from patients with Parkinson Criteria for rating – disease (PD) and controls using liquid chromatography mass spectrometry. therapeutic and diagnostic studies Methods NPub.org/coe Levels of caffeine and its 11 metabolites in serum from 108 patients with PD and 31 age- matched healthy controls were examined by liquid chromatography–mass spectrometry. RELATED ARTICLE Mutations in caffeine-associated genes were screened by direct sequencing. Editorial Results Caffeine and Parkinson Serum levels of caffeine and 9 of its downstream metabolites were significantly decreased even disease: A possible in patients with early PD, unrelated to total caffeine intake or disease severity. No significant diagnostic and pathogenic genetic variations in CYP1A2 or CYP2E1, encoding cytochrome P450 enzymes primarily breakthrough involved in metabolizing caffeine in humans, were detected compared with controls. Likewise, Page XXX caffeine concentrations in patients with PD with motor complications were significantly de- creased compared with those without motor complications.